BioInvent Announces Positive Phase 1 Data for BI-1206 in Combination with Pembrolizumab in Solid Tumors

Analysis reveals significant industry trends and economic implications

Release Date

2025-06-11

Category

Clinical Trial Event

Reference

Source

Breakthrough Clinical Results

BioInvent International AB announced positive Phase 1 data for its drug candidate BI-1206, used in combination with Merck's KEYTRUDA (pembrolizumab), in patients with heavily pre-treated solid tumors. The data showed encouraging clinical activity, including one complete response and one long-lasting partial response. Based on these results, BioInvent plans to launch a Phase 2a study to investigate BI-1206 in combination with pembrolizumab as a first-line treatment for patients with advanced or metastatic non-small cell lung cancer (NSCLC) and uveal melanoma. The Phase 2a study is expected to begin in the second half of 2025. BI-1206 is designed to enhance the effect of anti-PD-1 therapies by blocking FcγRIIB, a common resistance mechanism in cancer.

Key Highlights

  • Positive Phase 1 data for BI-1206 in combination with pembrolizumab showed encouraging clinical activity in solid tumors.
  • One complete response and one long-lasting partial response were observed.
  • BioInvent plans to initiate a Phase 2a study in first-line NSCLC and uveal melanoma patients.
  • The Phase 2a study is expected to start in H2 2025.

Incidence and Prevalence

Global NSCLC Incidence and Mortality (2022):

  • Lung cancer (including NSCLC and SCLC) was the most frequently diagnosed cancer in males worldwide in 2022, with an estimated 1.57 million new cases (95% UI: 1.56-1.58 million). In females, lung cancer was the second most diagnosed cancer (after breast cancer), with 0.91 million new cases (95% UI: 0.90-0.91 million).
  • Lung cancer was also the leading cause of cancer death in both males (1.23 million deaths; 95% UI: 1.22-1.24 million) and females (0.67 million deaths; 95% UI: 0.66-0.67 million).

  • NSCLC accounts for approximately 85% of all lung cancer cases. Applying this percentage to the 2022 GLOBOCAN estimates, we can approximate the global incidence of NSCLC:

  • Males: 1.57 million total lung cancers * 0.85 ≈ 1.33 million NSCLC cases

  • Females: 0.91 million total lung cancers * 0.85 ≈ 0.77 million NSCLC cases

NSCLC Prevalence:

GLOBOCAN does not provide prevalence data specifically for NSCLC. Prevalence is the number of people living with a disease at a given time, and it's influenced by both incidence and survival rates. Given the relatively poor survival rates for lung cancer, the prevalence is expected to be lower than the incidence.

US NSCLC Incidence and Prevalence (2010-2017):

  • Between 2010 and 2017, there were 1.28 million new NSCLC cases recorded in the US. The overall incidence per 100,000 persons decreased from 46.4 to 40.9. However, stage I incidence increased, likely due to improved detection of incidental nodules.
  • From 2010 to 2016, NSCLC prevalence per 100,000 persons in the US increased from 175.3 to 198.3. This increase was observed in younger patients but not in older patients.

Key Factors Influencing NSCLC Epidemiology:

  • Tobacco smoking remains the primary risk factor for lung cancer, including NSCLC.
  • Other risk factors include radon exposure, air pollution, and occupational exposures.
  • Improvements in early detection through lung cancer screening programs can lead to increased incidence of early-stage NSCLC.
  • Advances in treatment have contributed to improved survival rates and, consequently, increased prevalence.

It's important to note that these are estimates, and the actual numbers may vary. Furthermore, there can be regional differences in NSCLC incidence and prevalence due to variations in risk factors, access to healthcare, and screening practices.

Unmet Needs and Target Populations in NSCLC Research (Past 3 Years)

Research in Non-Small Cell Lung Cancer (NSCLC) continues to address several unmet needs, focusing on specific populations and challenges:

1. Second-Line Therapies for Advanced/Metastatic NSCLC:

A major unmet need is the development of effective second-line therapies for advanced or metastatic NSCLC, particularly for patients who develop resistance to first-line immunotherapy and targeted therapies. This includes research into:

  • Anti-angiogenic drugs: Such as ramucirumab combined with chemotherapy (docetaxel).
  • Antibody-drug conjugates (ADCs): Targeting specific tumor antigens.
  • Immunotherapies: Including CAR-T cell therapy and T-cell receptor therapy.
  • mRNA vaccines: To induce robust immune responses against cancer-specific antigens.
  • Tumor microenvironment: Exploring the role of neutrophils, macrophages, and targets like Smad3.

2. Targeted Therapies and Biomarker Development:

While targeted therapies have shown promise, there's a need for:

  • More precise biomarkers: To optimize treatment response and personalize treatment selection, especially for ADCs and bispecific antibodies.
  • Improved understanding of resistance mechanisms: To overcome resistance to targeted therapies caused by genetic alterations in cancer drivers (e.g., EGFR, ALK, ROS1).
  • Real-time mutation tracking: Using liquid biopsies to monitor for mutations like EGFR T790M and enable timely therapeutic adjustments.

3. Addressing Supportive Care Needs:

Beyond treatment efficacy, research also focuses on addressing unmet supportive care needs for advanced cancer patients and their caregivers, including:

  • Financial burdens: Associated with cancer treatment.
  • Health system and information needs: Access to reliable information and care.
  • Psychological support: Managing distress, depression, and anxiety related to the disease.
  • Physical and daily living needs: Addressing practical challenges posed by the disease.

4. Specific Patient Populations:

Research targets specific NSCLC patient populations, including:

  • Patients with HER2 alterations: This group has limited approved targeted therapies, and research is exploring ADCs and novel TKIs for HER2 mutations (exon 20), amplifications, and overexpression.
  • Patients with oncogenic mutations: Studies explore the experiences and unmet needs of patients with advanced or metastatic NSCLC driven by oncogenic mutations in genes like ALK, EGFR, and ROS1. These needs include viewing their disease as chronic, living meaningful lives without financial devastation, receiving emotional support, and being treated holistically as informed partners in their care.
  • Non-oncogene-driven NSCLC: For this group, chemotherapy remains the standard of care, but research is exploring new therapeutic strategies, including immunotherapy, to improve outcomes and address the limitations of current treatments.
  • Stage III NSCLC: This heterogeneous group requires multidisciplinary evaluation to determine optimal management, and research is addressing critical issues not covered by current trials and guidelines, such as pulmonary and cardiac toxicity, radiotherapy parameters, and treatment for unfit/elderly patients.

5. Ongoing Challenges:

Despite advancements, challenges remain in:

  • Drug sequencing and combination therapies: Determining the optimal sequence and combinations of targeted therapies and immunotherapies.
  • Toxicity management: Minimizing side effects associated with treatments.
  • Health equity: Addressing disparities in access to care and outcomes among different racial groups.

By focusing on these unmet needs and target populations, NSCLC research strives to improve patient outcomes, quality of life, and overall survival.

BI-1206 in combination with pembrolizumab is being investigated in several clinical trials for various cancer types beyond NSCLC. While specific intervention models vary depending on the trial and cancer type, some common themes emerge:

Advanced Solid Tumors:

  • Dose Escalation/Expansion: Many trials, especially in the early phases (Phase 1/2), utilize a dose escalation/expansion design. This involves starting with a low dose of BI-1206 and pembrolizumab and gradually increasing it to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D). Once the RP2D is established, the trial expands to include more patients to further evaluate safety and preliminary efficacy. This model is used to establish the safety profile and identify potential efficacy signals across a range of solid tumors.

Specific Cancer Types:

  • Microsatellite Instability-High (MSI-H)/Mismatch Repair Deficient (dMMR) Cancers: BI-1206, as an immune modulator, is being explored in combination with pembrolizumab for MSI-H/dMMR cancers. These cancers are characterized by defects in DNA repair mechanisms, leading to a high number of mutations and increased susceptibility to immunotherapy. The intervention model typically involves administering BI-1206 and pembrolizumab in combination, often after progression on prior therapies, including immunotherapy. The rationale is that BI-1206 may enhance the immune response against these tumors, overcoming resistance to prior immunotherapy.

  • Ovarian Cancer: Trials are investigating BI-1206 and pembrolizumab in combination with chemotherapy or other targeted therapies for recurrent ovarian cancer. Intervention models may involve adding BI-1206 and pembrolizumab to standard chemotherapy regimens or using them in combination after progression on prior therapies. The goal is to enhance the immune response and improve outcomes in this difficult-to-treat cancer.

  • Other Cancers: BI-1206 and pembrolizumab are also being studied in other cancer types, including endometrial cancer, head and neck squamous cell carcinoma, and melanoma. Intervention models vary depending on the specific cancer and trial design, but often involve combination therapy in patients with advanced or recurrent disease.

Overall, the intervention models for BI-1206 and pembrolizumab trials often involve:

  • Combination Therapy: BI-1206 is primarily being studied in combination with pembrolizumab, aiming to synergistically enhance anti-tumor immunity.
  • Advanced/Recurrent Disease: Most trials focus on patients with advanced or recurrent cancers who have limited treatment options.
  • Biomarker-Driven Patient Selection: Some trials incorporate biomarker-based patient selection, such as PD-L1 expression or MSI-H/dMMR status, to identify patients most likely to benefit.
  • Evaluation of Safety and Efficacy: Trials assess both the safety profile (e.g., adverse events) and efficacy (e.g., response rates, progression-free survival, overall survival) of the combination therapy.

It's important to note that the information provided here is based on general trends observed in clinical trials. Specific intervention models and eligibility criteria can vary significantly between different trials. Consulting clinical trial registries (e.g., ClinicalTrials.gov) is crucial for obtaining detailed information about specific trials.